We previously measured regional cerebral blood flow (rCBF) with oxygen-15 water and positron emission tomography in normal subjects during tasks involving working memory and found that most activate a cortical network including dorsolateral prefrontal cortex, superior parietal cortex (particularly the inferior parietal lobule), and inferior temporal cortex. During more complex tasks the hippocampus is also activated. We also previously showed that the acquisition, but not the retrieval of spatial data involves the frontal cortex, particularly on the right. We have now shown that word generation during semantic versus phonologic cues activated several similar brain regions including anterior cingulate, left frontal cortex, thalamus and cerebellum. Phonological fluency activated Brodmann areas 40 and 44 relatively more than semantic fluency, while semantic fluency was associated with relatively more blood flow in left temporal cortex than phonological fluency Studies of normal monozygotic twins aimed at determining the degree of heritability of cognitively-related regional brain function had suggested that while there are more similarities between twins than between age and sex-matched unrelated individuals, the degree of genetic influence may not be large. A new comparison with normal dizygotic twins has allowed the relative contributions of heritability and common environmental effects on cognitively-related rCBF to be calculated. The results to date indicate that the contributions of both environmental and hereditary factors to rCBF pattern are greater than to rCBF level. Very recently we have also found that several different pathophysiological mechanisms underly cognitive changes that occur in normal aging. In regions where physiological activity is normally suppressed when young subjects perform the tasks older subjects activate more, and, moreover, the more they activate (or fail to suppress), the worse they perform on the tasks. In other areas, where physiological activity is normally increased in young people performing the tasks, older subjects activate less; and the less they activate these regions, the more impaired their performance.